Biochemical characterization of the Sec14-PH module from the neurofibromatosis type I protein [Elektronische Ressource] / presented by Stefan Welti

Dissertationsubmitted to theCombined Faculties for the Natural Sciences and for Mathematicsof the Ruperto-Carola University of Heidelberg, Germanyfor the degree ofDoctor of Natural Sciencespresented byStefan Welti, Diplom-Biologeborn in: HeidelbergOral exam:Biochemical Characterizationof the Sec14-PH Modulefrom the Neurofibromatosis Type I ProteinReferees: PD Dr. Klaus ScheffzekProf.Dr. Michael BrunnerCONTENTSContents1 Abstracts 81.1 Abstract . . . . . . . . . . . . . . . . . . . . . . . . . . . 81.2 Zusammenfassung . . . . . . . . . . . . . . . . . . . . . . 92 Abbreviations 103 Introduction 133.1 Neurofibromatosis Type I . . . . . . . . . . . . . . . . . 133.2 The NF1 gene . . . . . . . . . . . . . . . . . . . . . . . . 143.3 Animal models of NFI . . . . . . . . . . . . . . . . . . . 153.3.1 Mouse . . . . . . . . . . . . . . . . . . . . . . . . 153.3.2 Drosophila melanogaster . . . . . . . . . . . . . . 163.4 The NF1 gene product Neurofibromin . . . . . . . . . . . 173.4.1 The GAP related domain and Ras. . . . . . . . . 203.4.2 The tubulin binding region . . . . . . . . . . . . . 233.4.3 The syndecan binding region . . . . . . . . . . . . 253.4.4 The CSRD domain . . . . . . . . . . . . . . . . . 263.4.5 The Sec14 homology - PH like module . . . . . . 273.5 Current situation and goals . . . . . . . . . . . . . . . . 294 Results and discussion 314.1 Improved overlay assays and PIP binding . . . . . . . . . 314.1.